Primary ImmunodeficiencyPhase 3NCT00278954

Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.

A Phase 3 study testing Gammaplex (Intravenous immunoglobulin) in people with Primary Immunodeficiency and Common Variable Hypogammaglobulinemia, run by Bio Products Laboratory at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 3 years and older
Conditions the study is for: Primary Immunodeficiency, Common Variable Hypogammaglobulinemia, X-linked Hypogammaglobulinemia
What is being tested?: Gammaplex (Intravenous immunoglobulin)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 7 sitesUnited States
Study dates: Jan 2006to Nov 2007
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

1. The subject is 3 years of age or older, of either sex, belonging to any ethnic group, and above a minimum weight of 27.5 kg. This weight is based on the amount of blood required for testing. If subject is participating in the PK segment, the minimum weight required is 37 kg.
2. The subject has a primary immunodeficiency disease, which has as a significant component of hypogammaglobulinemia and/or antibody deficiency (e.g. (exempli gratia / for example), common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-immunoglobulin M (hyper-IgM) syndrome, Wiskott-Aldrich Syndrome). Isolated deficiency of a single IgG subclass, or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion.
3. The subject has been receiving licensed or investigational (Phase III or IIIb) immunoglobulin intravenous (IGIV) replacement therapy at a dose that has not changed by + 50% of the mean dose for at least 3 months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be between 21 and 28 days inclusive. The subject must have maintained a trough level at least 300 mg/dL (milligram per decilitre) above baseline serum IgG levels (defined as before initiation of any gamma globulin treatment for that subject). The trough level must be 600 mg/dL.
4. Trough levels of IgG and dose of IGIV, treatment intervals, and the trade name of the IGIV treatments used for the last 2 consecutive routine (licensed or investigational product) must be documented for each subject before the first infusion in this study can be administered.
5. If a subject is a female of child-bearing potential, she must have a negative result on an Human Chorionic Gonadotrophin (HCG)-based pregnancy test.
6. If a subject is a female who is or becomes sexually active, she must practice contraception by using a method of proven reliability for the duration of the study.
7. The subject is willing to comply with all aspects of the protocol, including blood sampling, for the duration of the study.
8. The subject has signed an informed consent form (if at least 18 years old) or the subject's parent or legal guardian has signed the informed consent form. If appropriate, the subject has signed a child assent form (See Section 12.3).

Who cannot join

Subjects will be excluded if any of the following exclusion criteria are met:
The subject has a history of any severe anaphylactic reaction to blood or any blood-derived product.
The subject is known to be intolerant to any component of GAMMAPLEX, such as sorbitol (i.e.(id est / that is) , intolerance to fructose).
The subject has selective immunoglobulin A (IgA) deficiency, history of reaction to products containing IgA, or has a history of antibodies to IgA.
Subjects who have completed the study and subjects who have withdrawn cannot participate in the study for a second time.
The subject is currently receiving, or has received, any investigational agent, other than an immune serum globulin (ISG) preparation that is being evaluated in a Phase III or IIIb study, within the prior 3 months.

Show all 26Show fewer

The subject has been exposed to blood or any blood product or derivative within the last 6 months, other than a commercially available IGIV or other forms of commercially available and licensed ISG or an ISG product that is in Phase III or IIIb studies.
The subject is pregnant or is nursing.
The subject is positive for any of the following at screening:
Serological test for Human immunodeficiency virus (HIV) 1\&2, Hepatitis C virus (HCV), or Hepatitis B surface antigen (HBsAg)
Nucleic Acid test (NAT) for HCV
NAT for HIV
The subject, at screening, has levels greater than 2.5 times the upper limit of normal as defined at the central laboratory of any of the following:
Alanine transaminase (ALT)
Aspartate transaminase (AST)
The subject has a severe renal impairment (defined as serum creatinine greater than 2 times the upper limit of normal or Blood urea nitrogen (BUN) greater than 2.5 times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; the subject has a history of acute renal failure.
The subject is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.
The subject has a history of deep vein thrombosis (DVT), or thrombotic complications of IGIV therapy.
The subject suffers from any acute or chronic medical condition (e.g., renal disease or predisposing conditions for renal disease, coronary artery disease, or protein losing state) that, in the opinion of the investigator, may interfere with the conduct of the study.
The subject has an acquired medical condition, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (Absolute neutrophil count (ANC) < 1000 x 109/L).
The subject is receiving the following medication:
Immunosuppressive drugs
The subject is receiving the following medication: Steroids (long-term daily, >0.15 mg /kg/day of prednisone or prednisolone of equivalent dose of other corticosteroids) The requirement for burst or intermittent courses would not exclude the subject.
Immunomodulatory drugs
The subject has non-controlled arterial hypertension (systolic blood pressure > 160 mmHg (millimeters of mercury) and/or diastolic blood pressure > 100 mmHg).
The subject has anemia (hemoglobin < 10 g/dL) at screening.

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Family Allergy and Asthma Center PC
Atlanta, Georgia, 30342
Childrens Hospital at Buffalo, Allergy Division
Buffalo, New York, 14222
Rush University Medical Centre, University Consultants in Allergy & Immunology
Chicago, Illinois, 60612
Allergy, Asthma & Immunology Clinic, P.A.
Irving, Texas, 75063
UCLA Medical Centre
Irving, Texas, 75063
Allergy Associates of the Palm Beaches
North Palm Beach, Florida, 33408
University of Washington School of Medicine, Dept. of Pediatrics
Seattle, Washington, 989109-5235

Other trials in United States

About this study

Official title: A Phase III, Multicenter, Open-Label Study To Evaluate The Efficacy, Safety, and Pharmacokinetics of Gammaplex® in Primary Immunodeficiency Diseases

The main objective of this study is to see if GAMMAPLEX is efficacious with respect to Food and Drug Administration (FDA) minimal requirements (no more than 1 serious, acute, bacterial infection per subject per year) in subjects with Primary Immunodeficiency Diseases (PID). The secondary objectives are to assess the safety and tolerability of GAMMAPLEX and to determine if GAMMAPLEX has a pharmacokinetic (PK) profile comparable with that of intact Immunoglobulin G (IgG) in subjects with PID.

Read the detailed description

Primary Efficacy Variable The primary variable is the number of serious, acute, bacterial infections/subject/year, and it will be based on the total of all of the following events as defined by the FDA: bacterial Pneumonia, bacteremia/sepsis, osteomyelitis/septic arthritis, visceral abscess, and bacterial meningitis.

Secondary Efficacy Variables Secondary efficacy will be determined by using the following variables: number of days of work/school missed because of infection per subject year; number and days of hospitalizations because of infection per subject year; number of visits to physicians for acute problems and/or number of visits to hospital emergency rooms per subject year; other infections documented by fever or a positive result on a radiograph and/or culture; number of infectious episodes per subject per year; number of days on therapeutic antibiotics.These data will be entered into the subject diary, confirmed by the physician, and entered on the electronic-CRF (e-CRF).

Safety Variables. The variables used to assess safety will be the following: adverse events (AEs); vital signs; clinical laboratory tests and Direct Coombs' Test; transmission of viruses; physical examination.

Test product, dose/mode of administration, batch number(s): The GAMMAPLEX dose is 300-800 mg/kg/infusion (milligram per killgram per infusion) every 21 or 28 days, intravenously. At least 2 batches will be used in this study and no more than 1 batch in any given infusion.

Duration of treatment:

The total duration of treatment is 12 months.

Conditions: Primary Immunodeficiency, Common Variable Hypogammaglobulinemia, X-linked Hypogammaglobulinemia, Hypogammaglobulinemia, Immunodeficiency With Hyper-IgM, Wiskott-Aldrich Syndrome
Being tested: Gammaplex (Intravenous immunoglobulin)
Keywords: Primary Antibody Deficiency, Common variable hypogammaglobulinemia, X-linked hypogammaglobulinemia, Hypogammaglobulinemia, Immunodeficiency with hyper-IgM, Wiskott-Aldrich Syndrome
Medical subject headings: Primary Immunodeficiency Diseases, Common Variable Immunodeficiency, Hypogammaglobulinemia, X-Linked, Agammaglobulinemia, Hyper-IgM Immunodeficiency Syndrome, Wiskott-Aldrich Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Gammaplex (Intravenous immunoglobulin)Biological
GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously for 12 months.

Study groups in NCT00278954
Study group	Role	What they receive
Gammaplex	Other	Gammaplex Receives: Biological: Gammaplex (Intravenous immunoglobulin)

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease.
By assessing the number of serious, acute, bacterial infections per subject per year in subjects with Primary Immunodeficiency disease.
Measured: 12 months

Secondary outcomes (4)

The Pharmacokinetic (PK) Half-Life of Immunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Measured: -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days
The Pharmacokinetic (PK) Clearance of Immunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Measured: -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days
The Pharmacokinetic (PK) Volume of Distribution (Vz)of Immunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Measured: -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days
The Pharmacokinetic (PK) Mean Residence Time (MRT) for Inmuunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Measured: -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2006Nov 2007

First posted19 Jan 2006 (estimated)
Study startJan 2006
Primary completionNov 2007
Study completionNov 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Primary ImmunodeficiencyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00278954
Sponsor's protocol ID: GMX01
Status last verified: Jan 2013
First submitted: 18 Jan 2006
Last updated: 24 Jan 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Geng B, Clark K, Evangelista M, Wolford E. Low rates of headache and migraine associated with intravenous immunoglobulin infusion using a 15-minute rate escalation protocol in 123 patients with primary immunodeficiency. Front Immunol. 2023 Feb 2;13:1075527. doi: 10.3389/fimmu.2022.1075527. eCollection 2022.
PubMed 36818468

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Primary Immunodeficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Multicenter, Open-Label Study To Evaluate The Efficacy, Safety, and Pharmacokinetics of Gammaplex® in Primary Immunodeficiency Diseases
ClinicalTrials.gov ID: NCT00278954
Acronym / sponsor ID: GMX01
Conditions: Primary Immunodeficiency, Common Variable Hypogammaglobulinemia, X-linked Hypogammaglobulinemia, Hypogammaglobulinemia, Immunodeficiency With Hyper-IgM, Wiskott-Aldrich Syndrome
Keywords: Primary Antibody Deficiency, Common variable hypogammaglobulinemia, X-linked hypogammaglobulinemia, Hypogammaglobulinemia, Immunodeficiency with hyper-IgM, Wiskott-Aldrich Syndrome
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: Bio Products LaboratoryUniversity, hospital or other
Study start: Jan 2006
Primary completion: Nov 2007 (actual)
Study completion: Nov 2007 (actual)
First posted: 19 Jan 2006 (estimated)
Results: Posted 28 Jan 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Duration of treatment:

The total duration of treatment is 12 months.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Gammaplex	Other	Biological: Gammaplex (Intravenous immunoglobulin)Gammaplex

Who may qualify

Ages: 3 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

1. The subject is 3 years of age or older, of either sex, belonging to any ethnic group, and above a minimum weight of 27.5 kg. This weight is based on the amount of blood required for testing. If subject is participating in the PK segment, the minimum weight required is 37 kg.
2. The subject has a primary immunodeficiency disease, which has as a significant component of hypogammaglobulinemia and/or antibody deficiency (e.g. (exempli gratia / for example), common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-immunoglobulin M (hyper-IgM) syndrome, Wiskott-Aldrich Syndrome). Isolated deficiency of a single IgG subclass, or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion.
3. The subject has been receiving licensed or investigational (Phase III or IIIb) immunoglobulin intravenous (IGIV) replacement therapy at a dose that has not changed by + 50% of the mean dose for at least 3 months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be between 21 and 28 days inclusive. The subject must have maintained a trough level at least 300 mg/dL (milligram per decilitre) above baseline serum IgG levels (defined as before initiation of any gamma globulin treatment for that subject). The trough level must be 600 mg/dL.
4. Trough levels of IgG and dose of IGIV, treatment intervals, and the trade name of the IGIV treatments used for the last 2 consecutive routine (licensed or investigational product) must be documented for each subject before the first infusion in this study can be administered.
5. If a subject is a female of child-bearing potential, she must have a negative result on an Human Chorionic Gonadotrophin (HCG)-based pregnancy test.

Key exclusion criteria (26 listed)

Subjects will be excluded if any of the following exclusion criteria are met:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Gammaplex (Intravenous immunoglobulin)GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously for 12 months.	Biological	Gammaplex

Primary outcome

Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease.
Time frame: 12 months
By assessing the number of serious, acute, bacterial infections per subject per year in subjects with Primary Immunodeficiency disease.

4 secondary outcomes

The Pharmacokinetic (PK) Half-Life of Immunoglobulin G (IgG)
Time frame: -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days
The Pharmacokinetic (PK) Clearance of Immunoglobulin G (IgG)
Time frame: -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days
The Pharmacokinetic (PK) Volume of Distribution (Vz)of Immunoglobulin G (IgG)
Time frame: -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days
The Pharmacokinetic (PK) Mean Residence Time (MRT) for Inmuunoglobulin G (IgG)
Time frame: -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days

Results and safety

Results posted to the registry on 28 Jan 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Gammaplex	50	45

Primary outcome: Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease.

Time frame: 12 months. Number. Unit: SABIs/subject/year

Measure	Gammaplex n = 50
Value	0

Gammaplex: SABI per subject per year: 0 (99% CI 0 to 0.101), p = 0.01, Poisson regression with log link

Population analysed: Intent to Treat (ITT).

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: An event was only included in the analysis of Adverse Events (AEs) if it had an onset date between the first Gammaplex infusion and 30 days after the last Gammaplex infusion, inclusive.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Gammaplex	6 of 50 (12%)	47 of 50 (94%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36818468Geng B, Clark K, Evangelista M, Wolford E. Low rates of headache and migraine associated with intravenous immunoglobulin infusion using a 15-minute rate escalation protocol in 123 patients with primary immunodeficiency. Front Immunol. 2023 Feb 2;13:1075527. doi: 10.3389/fimmu.2022.1075527. eCollection 2022.
Sponsor websiteLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Melvin Berger, MD principal investigator

Rainbow Babies & Children's Hospital, Cleveland, Ohio

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jan 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease. (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00278954, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2013.